In this proposal, modulation and control of blast cell proliferation in acute myelogenous leukemia (AML) by humoral agents will be examined. In addition, effects of humoral agents on differentiation of blast cells will be assessed. Blast cell proliferation will be studied using blast colony forming assays (blast CFC), and 3H-TdR incorporation in liquid culture. Target population will include leukemia cell lines derived from patients which myeloid leukemias, and peripheral blood and bone marrow from patients with AML. Cell cycle status of blast CFC will be studied by thymidine suicide and cell cycle status of other populations by flow microfluoremetry. Differentiation will be assessed by loss of self-renewal capacity of blast CFC, histochemistry, phagocytosis, and monoclonal antibodies to cell surface antigens. The actions of the following homoral agents will be examined: 1)\prostaglandins 2)\cyclic nucleotides 3)\steroid hormones 4) colony stimulating factor (CSF) 5) media conditioned by PHA-stimulated mononuclear cells 6) erythropoietin and 7) media conditioned by HL60 promyelocytic leukemia cells. The latter appears to contain a new growth factor specific for blast cells which we will characterize during these studies. Multiple sources of CSF will be studied, and the action of these materials contrasted to that of PHA-LCM. The actions of the CSF preparations and LS60 CM on leukemia blasts will be contrasted to effects on normal granulocyte macrophage progenitors. These studies represent a continuing series of investigatios in humoral control of normal and abnormal myeloid cell proliferation. Such studies will provide insight into